Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:

TFV, TFV-DP, FTC, FTC-TP in blood, CVF, cervical and vaginal and rectal tissue over 14 days [ Time Frame: 14 days ] [ Designated as safety issue: No ]

The study aims to examine intra- and extracellular tenofovir and emtricitabine concentrations in various human compartments after a single dose, and to look at the potential for HIV infectivity in tissue samples from these compartments.

An estimated 80% of HIV infections worldwide are acquired through sexual transmission.1 Viable methods of preventing the sexual transmission of HIV are urgently needed, especially in resource-poor countries. As these countries now have increased access to generic antiretroviral medications, oral administration of antiretroviral drugs as pre-exposure prophylaxis may serve as a feasible, minimally invasive mechanism of preventing the sexual transmission of HIV globally.

Antiretroviral prophylaxis with the combination of tenofovir and emtricitabine has recently been investigated by the U.S. Centers for Disease Control and Prevention in a series of studies with rhesus macaques. Researchers developed a rectal inoculation model using concentrations of Simian HIV (SIV) that were representative of HIV exposure in humans. With this model, researchers demonstrated that standard doses of tenofovir disoproxil fumarate delayed, or partially protected, animals from the acquisition of Simian HIV during a 14-week time period. In this same model, high dose tenofovir was fully protective from infection.2 However, it is unknown how concentrations in the macaque mucosal surfaces compare to that in humans. Notwithstanding, a number of clinical studies are currently investigating daily dosing of tenofovir or tenofovir with emtricitabine for pre-exposure prophylaxis.3

Since daily dosing of antiretrovirals for pre-exposure prophylaxis is not sustainable long-term, other coitally-dependent (episodic) dosing strategies are needed. However, the extent to which these drugs concentrate in tissues, and the duration of intracellular phosphate exposure after single doses, is currently unknown. This information is required to inform the potential of success with these dosing strategies.

At steady-state concentrations, the mean blood plasma half-life (t½) of tenofovir and emtricitabine are 15.9 hours and 10.7 hours, respectively. 4 However, the intracellular t½ of tenofovir diphosphate and emtricitabine triphosphate are >60 hours and 39 hours, respectively.5 The long intracellular t½ of the active forms of these drugs might hold advantages for episodic dosing. However, the long t½ might also hold disadvantages in terms of the development of viral resistance mutations. This phenomenon (the development of resistance after a single dose of a long t½ drug), has been previously seen with nevirapine given during delivery to HIV-infected women to prevent mother to child transmission of HIV.6 However, these women were chronically infected, rather than newly infected, as would be the case with populations exposed to prevention strategies.

The proposed study aims to augment the information gathered in previous studies by examining intracellular and extracellular tenofovir and emtricitabine drug concentrations in various human compartments after a single dose, and to describe the potential for HIV infectivity in selected tissue samples obtained from these compartments.

Eligibility

Ages Eligible for Study:

18 Years to 49 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Sampling Method:

Non-Probability Sample

Study Population

Twelve adult (18 years or older) healthy volunteers will be recruited to participate in the study. A total of 6 men and 6 women will be enrolled. Subjects of all races and ethnicities may participate, provided they meet study inclusion/exclusion criteria.

Criteria

Inclusion Criteria:

Must be above 18 years of age and less than 50 years of age

Able and willing to provide written informed consent to take part in the study

Able and willing to provide adequate information for locator purposes

Must be in good general health by volunteer history without any clinically significant systemic disease, full physical examination including blood pressure and pulse rate measurement and clinical laboratory tests

HIV-1 status antibody negative as documented at screening

Able to comply with all study procedures throughout the duration of study participation

Able to comply with Lifestyle Guidelines throughout the duration of study participation

(Males Only)

Willing to abstain from any sexual activity including intercourse, masturbation, oral contact with the rectum, and insertion of anything per rectum for the entire duration of the study period.

Body Mass Index (BMI) of approximately 18 to 30 kg/m2; and a total body weight > 50 kg (110 lbs).

(Females Only)

Must be pre-menopausal

Must have an intact uterus and cervix

Must have a negative serum pregnancy test at screening

Must have negative urine pregnancy tests at day 7 and day 14

Must have regular menstrual cycles (minimum of 26 and maximum of 35 days)

Must be at least 2 months since last pregnancy outcome and have had at least two spontaneous menses

Body Mass Index (BMI) of approximately 18 to 30 kg/m2; and a total body weight > 50 kg (110 lbs).

Must abstain from use of intravaginal products including tampons, spermicides, lubricants, vaginal hygiene products, diaphragms, and cervical caps, for 72 hours prior to the baseline study visit and through 21 days after the baseline study visit.

Must abstain from any sexual activity including intercourse, oral contact with the female genitalia, masturbation, and penetration of the vagina by fingers, tampons, sex toys, or any other objects for 72 hours prior to the baseline study visit (Day 0) and through 19 days after the baseline study visit.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326221

Locations

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

University of North Carolina, Chapel Hill

Gilead Sciences

Investigators

Principal Investigator:

Angela DM Kashuba, PharmD

University of North Carolina

Principal Investigator:

Kristine B Patterson, MD

University of North Carolina

More Information

No publications provided

Responsible Party:

Angela Kashuba, PharmD, Professor, University of North Carolina, Chapel Hill